Pentaerithrityl tetranitrate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

A study performed in 2009 by the U.S. Army Center for Health Promotion and Preventive Medicine following the guidance USEPA OPPTS 870.3550 Reproduction/Developmental Toxicity Screening Test demostrated that rats (10 male and 10 female) orally dosed 100, 500 and 1000 mg/kg for 56 days did not show any effects on their reproductive performance. Due to explosive properties of the substance, no further testing could be conducted.

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Qualifier:

according to guideline

Guideline:

other: USEPA OPPTS 870.3550 Reproduction/Developmental Toxicity Screening Test

GLP compliance:

yes

Remarks:

This study was conducted consistent with the standards found in Title 40 US Code of Federal Regulations (CFR), Part 792, Good Laboratory Practices.

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

corn oil

Duration of treatment / exposure:

56 days

Frequency of treatment:

daily

Remarks:

Doses / Concentrations:0 mg PETN/kgBasis:nominal in diet

Remarks:

Doses / Concentrations:100 mg PETN/kgBasis:nominal in diet

Remarks:

Doses / Concentrations:500 mg PETN/kgBasis:nominal in diet

Remarks:

Doses / Concentrations:1000 mg PETN/kgBasis:nominal in diet

No. of animals per sex per dose:

10

Control animals:

yes

Parental animals: Observations and examinations:

DETAILED CLINICAL OBSERVATIONS: Yes - Time schedule: at least once a day, and more frequently when signs of toxicity are observed. The duration of gestation was recorded and calculated from day 0 of pregnancyBODY WEIGHT: Yes - Time schedule for examinations: Males and females were individually weighed the day before and on the first day of dosing, weekly thereafter, and at termination of the study.FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes - Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

Sperm parameters (parental animals):

PARAMETERS EXAMINED IN [MALE PARENTAL GENERATIONS [testis weight, epididymis weight, daily sperm production, sperm count in testes, sperm count in epididymides, enumeration of cauda epididymal sperm reserve, sperm motility, sperm morphology, other:]

Litter observations:

Each litter was examined as soon as possible after delivery to establish the number and sex of pups,still births, live births, and runts (pups that are significantly smaller than corresponding control pups), and the presence of gross abnormalities. Live pups were counted and sexed, and litters weighed within 24 hr of parturition (day 1) and on day 4 post-partum.

Postmortem examinations (parental animals):

SACRIFICE: No rats died due to PETN toxicityGROSS NECROPSY: animals were examined for any abnormalities or pathological changes, with special attention being paid to the reproductive organs.HISTOPATHOLOGY / ORGAN WEIGHTS: Testes, epididymides, and ovaries were fixed in Bouin�s fixative, embedded in paraffin, cut into transverse sections of 4�5 mm thickness, and stained with PAS and hematoxylin.

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

not examined

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Other effects:

no effects observed

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

Dose descriptor:

NOAEC

Effect level:

>= 1 000 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

Clinical signs:

effects observed, non-treatment-related

Dermal irritation (if dermal study):

not examined

Mortality / viability:

not examined

Body weight and weight changes:

not examined

Food consumption and compound intake (if feeding study):

effects observed, non-treatment-related

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings:

not examined

Other effects:

not specified

Behaviour (functional findings):

not specified

Developmental immunotoxicity:

not specified

Dose descriptor:

dose level: Pups received PETN only through lactation.

Generation:

F1

Effect level:

> 100 - < 500 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

body weight and weight gain

Reproductive effects observed:

not specified

Conclusions:

No adverse effects on development or reproduction from PETN exposure were observed.

Executive summary:

Sprague-Dawley rats were exposed to oral daily adjusted volumetric doses of 0, 100, 500, or 1,000mg PETN/kg body mass in a corn oil vehicle for up to 56 days. Mating, duration of gestation, body weight, feed consumption, overall condition of adults, and the number, sex, and condition of pups were recorded. Histological examinations were also performed on the ovaries, testes, and epididymides of animals from the control and the highest dose groups. Only body weights

and feed consumption were affected by treatment; however, these differences may be attributed more to volumetric adjustments of vehicle in the control and high-dose groups than to PETN toxicity. No adverse effects on development or reproduction from PETN exposure were observed.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Effects on developmental toxicity

Description of key information

Due to explosive properties of the substance, the performance of this test is highly advised against.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

PETN is a sensitive compound and is easily detonated by an appropriate mechanical shock or when it is exposed to heat. Submitting the substance to testing would pose an extreme risk to the laboratory personnel and facilities due to explosive nature of the substance.

Justification for classification or non-classification

Reliable information on toxicity for reproduction shows a NOAEL of > 1000 mg/kg bw/day. No classification is proposed based on the results obtained from studies performed.